The long term objective of this proposal is to define the mechanisms involved in lung IL-17A expression that result from respiratory syncytial virus (RSV) infection of mice that have ongoing allergic lung inflammation. Viral infections trigger the majority of acute asthma symptoms and RSV is an important cause of asthma exacerbations, particularly in children and the elderly. Most of these virus-induced asthma exacerbations occur in patients with airway allergic inflammation, but the exact mechanisms by which viral infection results in asthma symptoms and decline in lung function remain largely unknown. Compared to BALB/c mice that are allergically-sensitized and challenged with ovalbumin alone (OVA), or mice that are infected with RSV alone (RSV), mice that are RSV-infected during ongoing ovalbumin-induced allergic inflammation (OVA/RSV) have significant airway hyperresponsiveness (AHR) and augmented airway mucus expression. This synergistic increase in AHR and airway mucus present in OVA/RSV mice is strongly associated with increased expression of lung IL-17A protein, whereas there is negligible IL-17A in OVA mice and none in RSV mice. In Specific Aim 1, we will determine the responsible T cell population and the cytokine background necessary for increased lung IL-17A production in the setting of RSV infection and ovalbumin-induced pulmonary allergic inflammation. We will test this in Specific Aim 1 by determining the antigen-specific nature of the T cells responsible for lung IL-17A expression and the component of Th2 inflammation necessary for the OVA/RSV-induced lung IL-17A production. In Specific Aim 2, we will determine the role of specific dendritic cell subsets and their function in lung IL-17A expression in the setting of RSV infection during ongoing allergic airway inflammation. Specifically, we will determine if depletion of plasmacytoid dendritic cells results in an increase in OVA/RSV-induced IL-17A production in the lung. In addition, we will determine the effect of allergic antigen presentation by either plasmacytoid or myeloid dendritic cells and subsequent antigen challenge on RSV-induced lung IL-17A expression. Defining the mechanisms by which RSV-infection on an allergic background induces lung IL-17A production may provide potential therapeutic targets for reducing RSV-induced asthma exacerbations.